An observational study in Myasthenia Gravis (MG), Myasthenia Gravis Associated With Thymoma and Thymoma, sponsored by IRCCS San Raffaele. Not yet recruiting at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-06.
Sponsored by IRCCS San Raffaele · Observational
The goal of this observational study is to investigate the clinical, immunological, and neuromuscular features associated with the development and progression of myasthenia gravis (MG) in adult patients with thymic abnormalities and/or MG-related antibodies, including individuals with or without clinically manifest disease.
The main questions it aims to answer are:
Participants will:
Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction characterized by fluctuating muscle weakness and fatigability. In most cases, the disease is associated with antibodies directed against the acetylcholine receptor (AChR) and is frequently linked to thymic abnormalities, including thymoma and thymic hyperplasia. Despite the recognized role of the thymus in MG pathogenesis, the mechanisms driving the transition from thymic autoimmunity to clinically manifest disease remain incompletely understood, and reliable biomarkers for disease prediction and monitoring are lacking.
This study is a single-center, prospective, observational translational cohort designed to comprehensively characterize the clinical, neurophysiological, serological, immunological, and histopathological features of patients with thymic abnormalities and/or MG. The study adopts a multimodal approach integrating routine clinical assessments with advanced laboratory and tissue-based analyses, with the aim of identifying biological mechanisms and potential biomarkers associated with MG onset and progression.
A total of 40 adult participants will be enrolled and stratified into four predefined groups:
At baseline, all participants will undergo standardized clinical and neurological evaluation, including validated MG-specific outcome measures, neurophysiological testing (repetitive nerve stimulation and single-fiber electromyography), and blood sampling for serological and immunological analyses. Imaging assessments, including chest CT for thymic characterization and orbital MRI for evaluation of extraocular muscle involvement, will be performed according to clinical indications. Participants will be followed longitudinally for 18 months, with scheduled evaluations at 6, 12, and 18 months. Follow-up assessments will include repeated clinical, neurophysiological, and serological measurements to capture disease evolution over time and to evaluate the relationship between biological markers and clinical outcomes.
In participants undergoing thymectomy as part of standard clinical care, thymic tissue will be collected for routine diagnostic purposes, with additional samples used for research analyses. Residual intercostal muscle tissue obtained within the surgical field will also be collected, without modification of the surgical procedure or additional risk to the patient. These samples will be used to investigate structural and molecular features of the neuromuscular junction, including receptor organization and evidence of immune-mediated damage.
Peripheral blood samples collected at baseline and follow-up visits will be used to characterize systemic immune profiles, including autoantibodies, cytokines, and complement activation products. These data will be integrated with clinical, neurophysiological, and histopathological findings to explore associations with MG onset, severity, and progression.
In participants with established MG, longitudinal symptom monitoring will be performed using an electronic patient-reported outcome tool based on questionnaires routinely used in clinical practice. Patients will record daily symptoms across key domains (ocular, bulbar, respiratory, and limb involvement), enabling high-resolution assessment of symptom fluctuations over time. These data will be compared with clinical outcome measures collected during scheduled visits to evaluate concordance and the potential added value of continuous symptom monitoring.
Overall, this study aims to provide an integrated characterization of MG across clinical, biological, and tissue levels, with the ultimate goal of identifying early predictors of disease development and progression, improving risk stratification, and supporting future strategies for personalized monitoring and intervention.
330 studies on the registry are indexed under Myasthenia Gravis; 144 are open to participants now.
This study's planned enrollment of 40 is below the median of 130 across 105 observational studies indexed under Myasthenia Gravis.
Browse Myasthenia Gravis studies →IRCCS San Raffaele is the lead sponsor of 453 studies on the registry; 234 are open to participants now.
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The study population consists of adult patients (≥18 years) undergoing evaluation for thymic abnormalities and/or myasthenia gravis at a tertiary referral center. Participants include individuals with thymoma or other thymic pathology, with or without MG-related antibodies and with or without clinically manifest myasthenia gravis, as well as patients with established myasthenia gravis without evidence of thymic abnormalities.
Participants are recruited from routine clinical care settings, including neurology and thoracic surgery units, and reflect a spectrum of clinical and immunological phenotypes relevant to disease development and progression. This population enables the investigation of the relationship between thymic pathology, systemic immune profiles, and neuromuscular junction involvement in myasthenia gravis.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Participants must also meet the criteria for at least one of the following study groups:
Cohort 1: Thymoma with MG-related antibodies
Cohort 2: Other thymic abnormalities with MG-related antibodies
Cohort 3: Thymoma without MG-related antibodies
Cohort 4: Myasthenia gravis without thymic abnormalities
Established clinical diagnosis of myasthenia gravis with consistent clinical features, supported by at least one of the following:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with histologically or radiologically confirmed thymoma and presence of MG-related antibodies (AChR), with or without clinically manifest myasthenia gravis.
Patients with non-thymomatous thymic pathology (e.g., thymic hyperplasia) and presence of MG-related antibodies (AChR), with or without clinically manifest myasthenia gravis.
Patients with confirmed thymoma, negative for MG-related antibodies, and without clinical signs or diagnosis of myasthenia gravis.
Patients with an established diagnosis of myasthenia gravis based on clinical, serological, and/or neurophysiological criteria, and no evidence of thymic abnormalities.
Qualitative assessment of neuromuscular junction structural abnormalities in intercostal muscle samples
The primary outcome is the qualitative assessment of neuromuscular junction structural abnormalities in residual intercostal muscle samples collected from participants undergoing clinically indicated thymectomy. Neuromuscular junction integrity will be evaluated using histological, immunofluorescence, and ultrastructural analyses, including assessment of acetylcholine receptor clustering, IgG and complement deposition, postsynaptic fold morphology, and features of synaptic remodeling or immune-mediated injury. Structural abnormalities will be described in terms of presence or absence and, where applicable, semi-quantitative grading. Findings will be compared across participant groups according to thymic pathology, MG-related antibody status, and the presence or absence of clinically manifest myasthenia gravis.
Time frame: At the time of thymectomy (baseline)
Qualitative assessment of thymic histopathological features
Qualitative assessment of thymic histopathological features in thymic tissue collected from participants undergoing clinically indicated thymectomy. Thymic tissue will be evaluated for histopathological features including thymoma subtype, thymic hyperplasia, germinal centers, lymphoid infiltrates, and AIRE expression, where applicable. Histopathological findings will be described in terms of presence or absence and, where applicable, semi-quantitative grading. These features will be analyzed in relation to neuromuscular junction structural abnormalities identified in intercostal muscle samples, as well as according to MG-related antibody status and the presence or absence of clinically manifest myasthenia gravis.
Time frame: At the time of thymectomy (baseline)
Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) score
The MG-ADL is an 8-item scale assessing myasthenia gravis-related symptoms and functional impairment, with a total score ranging from 0 to 24. Higher scores indicate greater disease burden. Changes from baseline will be evaluated during follow-up and analyzed in relation to biological markers, neuromuscular junction findings, and electronically collected patient-reported symptom scores.
Time frame: Baseline, 6, 12, and 18 months
Change in Quantitative Myasthenia Gravis (QMG) score
The QMG is a 13-item examiner-administered scale assessing muscle weakness and fatigability, with a total score ranging from 0 to 39. Higher scores indicate greater disease severity. Changes from baseline will be evaluated during follow-up and analyzed in relation to biological markers, neuromuscular junction findings, and electronically collected patient-reported symptom scores.
Time frame: Baseline, 6, 12, and 18 months
Change in serum MG-related autoantibody levels over time
Measurement of serum levels of MG-related autoantibodies, including acetylcholine receptor (AChR) antibodies, assessed using cell-based assays and ELISA assays. Autoantibody levels will be reported as titers and evaluated at baseline and during follow-up to describe their distribution and longitudinal changes. These measurements will be analyzed in relation to clinical and neurophysiological findings, as well as thymyc histopathology and neuromuscular junction structural features.
Time frame: Baseline, 6, 12, and 18 months
Change in plasma and serum levels of complement activation products
The secondary outcome is the change in plasma and serum levels of complement activation products, including C3b, C5a, and sC5b-9, assessed using immunoassay-based methods. Changes in complement activation product levels will be evaluated from baseline to follow-up visits and reported as concentrations. These measurements will be analyzed in relation to clinical and neurophysiological findings, as well as thymic histopathology and neuromuscular junction structural features.
Time frame: Baseline, 6, 12, and 18 months
Change in mean daily composite MG symptom questionnaire score (electronically collected)
The electronic tool consists of a structured daily questionnaire in which patients report symptom severity across four domains (ocular, bulbar, respiratory, and limb involvement), using a visual analogue scale (VAS, 0-10 for each item; 0 = no symptoms, 10 = maximum severity). Individual item scores are summed to generate a daily composite score (range 0-40), with higher scores indicating greater symptom burden. The mean daily composite score will be calculated over predefined time intervals during follow-up, and changes from baseline will be evaluated longitudinally. The questionnaire is based on domains derived from the Myasthenia Gravis Activities of Daily Living (MG-ADL) instrument. Patient-reported scores will be compared with MG-ADL and Quantitative Myasthenia Gravis (QMG) scores assessed at scheduled visits to evaluate concordance and the ability to capture symptom fluctuations over time.
Time frame: Baseline and up to 18 months
Plan to share: No
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Start is estimated for Sep 2026; primary completion for Sep 2029, 35 months later.
Of 62 observational studies under Myasthenia Gravis, half reached primary completion within 52 months of starting (the median), counting those still running; a quarter within 24. This study's planned 35 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
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